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1.
The pharmacokinetics of diclofenac were compared after intravenous and oral administration at a dose of 5 mg/kg in a rat model of diabetes mellitus induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. Diclofenac was reported to be metabolized via the hepatic microsomal cytochrome P450 (CYP) 2C11 in male rats. The expression and mRNA level of CYP2C11 decreased in rat models of DMIA and DMIS. Hence, the time-averaged nonrenal clearance (Clnr) of diclofenac was expected to be slower in a rat model of diabetes. As expected, after intravenous administration, the Clnr values of diclofenac were significantly slower in rat models of DMIA (11.3 versus 13.6 ml/min/kg) and DMIS (8.06 versus 15.2 ml/min/kg) than those in control rats. As a result, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) values were significantly greater in rat models of DMIA (435 versus 367 microg min/ml) and DMIS (540 versus 329 microg min/ml). However, after oral administration, the AUC from time zero to the last measured time, 12 h, in plasma (AUC0-12 h) values were comparable between the rat models of DMIA and DMIS and their control rats, and this could be due to changes in the first-pass effect of diclofenac and was not due to a decrease in the absorption of diclofenac in the rat models of diabetes. 相似文献
2.
Pharmacokinetic parameters of chlorzoxazone (CZX) and its main metabolite, 6-hydroxychlorzoxazone (OH-CZX), were compared after intravenous (20 mg/kg) and oral (50 mg/kg) administration of CZX in rat model of diabetes induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. In both rat models of diabetes, the expression and mRNA level of CYP2E1 increased, and CZX was metabolized to OH-CZX via CYP2E1 in rats. Hence, it could be expected that formation of OH-CZX increased in both rat models of diabetes. As expected, after intravenous (80.5% and 74.4% increase in rat models of DMIA and DMIS, respectively) and oral (55.6% and 70.5% increase, respectively) administration of CZX, the AUC of OH-CZX was significantly greater than their respective control rats. Since, CZX is an intermediate hepatic extraction ratio drug, the greater AUC values of OH-CZX (the significantly faster CL(NR) of CZX) in both rat models of diabetes could be supported by significantly faster CL(int) for the formation of OH-CZX (75.9% and 129% increase for rat models of DMIA and DMIS, respectively) and significantly greater free fractions of CZX in plasma (51.9% and 58.9% increase, respectively). Also it was reported that hepatic blood flow rate was faster in male Wister rat model of DMIS. 相似文献
3.
Objectives In rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUC metabolite/AUC parent drug ratios, or the time‐averaged nonrenal and total body clearances (CL NR and CL, respectively) of parent drugs as reported in the literature have been compared. Key findings After intravenous administration of drugs that were mainly metabolized via hepatic CYP isozymes, their hepatic clearances were found to be dependent on the in‐vitro hepatic intrinsic clearance (CL int) for the disappearance of the parent drug (or in the formation of the metabolite), the free fractions of the drugs in the plasma, or the hepatic blood flow rate depending on their hepatic extraction ratios. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized via the kidney in DMIA or DMIS rats were dependent on the drugs. However, the biliary or renal CL values of drugs that were mainly excreted via the kidney or bile in DMIA or DMIS rats were faster. Summary Pharmacokinetic studies of drugs in patients with type I diabetes mellitus were scarce. Moreover, similar and different results for drug pharmacokinetics were obtained between diabetic rats and patients with type I diabetes mellitus. Thus, present experimental rat data should be extrapolated carefully in humans. 相似文献
4.
The area under the curve (AUC) of mirodenafil after intravenous administration in diabetes mellitus induced by streptozotocin (DMIS) rats was significantly smaller (by 28.0?%) than the control value, and the AUCSK3541/AUCmirodenafil ratio was significantly greater (by 130?%) in DMIS rats. This may be explained by the significantly faster hepatic CLint of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values. The AUC of mirodenafil after oral administration was comparable between DMIS and control rats, possibly because of the comparable intestinal CLint, which may be attributable to increased CYP1A2 expression and decreased CYP2D expression in the intestines of DMIS rats. 相似文献
5.
It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats, and the expression and mRNA levels of hepatic CYP2C11 and 3A1 decreased and increased, respectively, whereas the expression of CYP2D1 was not changed in rat model of diabetes induced by streptozotocin (DMIS). Also minimizing the toxic effects of streptozotocin by carrying out experiments 4-5 weeks after streptozotocin injection has been reported. Thus, the pharmacokinetics of metformin was evaluated in rat model of DMIS at the 7th and the 29th days after streptozotocin injection. After intravenous administration of metformin (100 mg/kg) to rat model of DMIS, the CL(R) became significantly faster (46.9% and 77.8% increase for the 7th and the 29th days, respectively; due to urine flow rate-dependent timed-interval renal clearance of the drug) and CL(NR) became significantly slower (28.0% and 34.3% decrease, respectively; due to decreased hepatic CYP2C11) than in their respective controls. After oral administration of metformin (100 mg/kg) to rat model of DMIS, the AUC became significantly smaller (18.6% and 33.7% decrease for the 7th and the 29th days, respectively) than in their respective controls. The CL(NR) of metformin were comparable between two rat models of DMIS. 相似文献
6.
It has been reported that diabetic patients have an increased risk of developing epileptic convulsions compared with the non-diabetic population, and phenytoin has widely been used for neuralgia in diabetic neuropathy. It has also been reported that in both diabetic rats induced by alloxan (DMIA rats) and by streptozotocin (DMIS rats), the protein expression and mRNA level of 2C11 decreased, but in DMIS rats, the protein expression of CYP2C6 increased. Thus, the pharmacokinetics of phenytoin and 4'-HPPH were investigated after intravenous or oral administration of phenytoin at a dose of 25 mg/kg to DMIA and DMIS rats. After intravenous or oral administration of phenytoin, the AUC (or AUC(0-12 h)) values of both phenytoin and 4'-HPPH were comparable (not significantly different) between each diabetic and the respective control rats. Although the exact reason is not clear, this could have been due to opposite protein expression (and/or mRNA levels) of CYP2C6 and 2C11 in diabetic rats. 相似文献
7.
The pharmacokinetic and pharmacodynamic parameters of torasemide were compared after intravenous administration at a dose of 2 mg/kg to diabetic rats induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. It was reported that torasemide was mainly metabolized via CYP2C11 in rats and the expression and mRNA level of CYP2C11 decreased in DMIA and DMIS rats. Hence, it could be expected that the time-averaged nonrenal clearance (Cl(nr)) of torasemide could be slower in the diabetic rats. As expected, the Cl(nr) values were significantly slower in DMIA (0.983 versus 1.35 ml/min/kg) and DMIS (0.998 versus 1.36 ml/min/kg) rats. However, the time-averaged renal clearance (Cl(r)) values of torasemide were significantly faster in DMIA (0.164 versus 0.0846 ml/min/kg) and DMIS (0.205 versus 0.0967 ml/min/kg) rats due to urine flow rate-dependent timed-interval Cl(r) of torasemide in rats. The comparable time-averaged total body clearance (Cl) values between the diabetic and control rats were due to partially compensated Cl(r) in the diabetic rats. The 8 h urine output and diuretic efficiency increased significantly in the diabetic rats due to significantly greater 8 h urinary excretion of unchanged torasemide and at least partly due to an increase in urine output in diabetes per se (without administration of any drugs). 相似文献
8.
Intravenous administration of DA-8159, 30 mg/kg, to rats with diabetes mellitus induced by streptozotocin (DMIS), AUC of DA-8164 (a metabolite) was significantly smaller in rats with DMIS (57.9 compared with 81.8 microg x min/mL). This may be due to more contribution of significantly faster clearance of DA-8164 than that of significantly greater formation of DA-8164 in the rats. For example, the CL of DA-8164 was significantly faster (9.68 compared with 6.29 mL/min/kg) after intravenous administration of DA-8164, 10 mg/kg, to rats with DMIS and in vitro intrinsic clearance for the formation of DA-8164 was significantly faster (1.92 compared with 1.59 microL/min/mg protein) in hepatic microsomal fraction of rats with DMIS due to significant increase in expression of CYP3A1(23) in the rats. DA-8164 was formed mainly via CYP3A1/2 in rats. After intravenous administration of DA-8159, renal clearance was significantly faster in rats with DMIS (5.79 compared with 2.80 mL/min/kg) due to urine flow-dependent renal clearance of DA-8159 in rats. After oral administration of DA-8159, the AUC values of both DA-8159 and DA-8164 were not significantly different between two groups of rats. Although the exact reason is not known it may be due to changes in first-pass effect of DA-8159 in rats with DMIS. 相似文献
9.
Rats with liver cirrhosis induced by N‐dimethylnitrosamine (LC) and rats with LC with diabetes mellitus induced by streptozotocin (LCD) have been developed as animal models for human liver cirrhosis and liver cirrhosis with diabetes mellitus, respectively. Changes in the pharmacokinetics of drugs (mainly non‐renal clearance, CLNR) in LC and LCD rats reported in the literature compared with respective control rats were reviewed. This review mainly explains the changes in the CLNRs of drugs (which are mainly metabolized via hepatic microsomal cytochrome P450s, CYPs) in LC and LCD rats, in terms of the changes in in vitro hepatic intrinsic clearance ( CLint; mainly due to the changes in CYPs in the disease state), free (unbound) fraction of a drug in the plasma ( fp) and hepatic blood flow rate ( QH) depending on the hepatic excretion ratio of the drug. Generally, changes in the CLNRs of drugs in LC and LCD rats could be well explained by the above‐mentioned three factors. The mechanism of urinary excretion of drugs (such as glomerular filtration or renal active secretion or reabsorption) in LC and LCD rats is also discussed. The pharmacokinetics of the drugs reported in the LC and LCD rats were scarce in humans. Thus, the present rat data should be extrapolated carefully to humans. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
10.
It was reported that the expression of CYP3A1 increased in rats with acute renal failure induced by uranyl nitrate (rat model of U-ARF) compared with controls. It was shown that telithromycin was mainly metabolized via CYP3A1/2 in rats in this study. Hence, the pharmacokinetic parameters of telithromycin were compared after both intravenous and oral administration at a dose of 50 mg/kg to control rats and a rat model of U-ARF. After intravenous administration of telithromycin to rats with U-ARF, the AUC and renal clearance (Cl(r)) were significantly greater (35.0% increase) and slower (99.1% decrease), respectively, than the controls. Unexpectedly, the nonrenal clearance (Cl(nr)) of telithromycin was comparable between the two groups of rats, suggesting that CYP3A isozyme responsible for the metabolism of telithromycin seemed not to be expressed considerably in the rat model of U-ARF. After oral administration of telithromycin to rats with U-ARF, the AUC was also significantly greater (127% increase) than the controls and the value, 127%, was considerably greater than 35.0% after intravenous administration of telithromycin. This may be due mainly to the decrease in the intestinal first-pass effect of telithromycin compared with controls in addition to significantly slower Cl(r) than controls. 相似文献
11.
The time-dependent (2-h, 24-h, and 96-h) effects of Escherichia coli lipopolysaccharide (ECLPS) on the intravenous (100?mg kg?1) and oral (100?mg kg?1) metformin pharmacokinetics were evaluated in rats. After the intravenous administration of metformin to 24-h and 96-h ECLPS rats, the total area under the plasma concentration–time curve from time zero to time infinity (AUCs) and time-averaged non-renal clearances (CLNRs) of metformin were significantly greater and slower, respectively, than the controls. However, after the oral administration of metformin, the AUCs of metformin were comparable among four groups of rats. The greater (slower) intravenous AUCs (CLNRs) of metformin in 24-h and 96-h ECLPS rats were due to the slower hepatic intrinsic clearance (CLint) because of a decrease in the protein expression of hepatic cytochrome P450 (CYP) 2C11 and/or CYP3A subfamily than controls. The comparable oral AUCs among four groups of rats were mainly due to the comparable gastrointestinal metabolism (CLint). 相似文献
12.
The pharmacokinetic parameters of 5-fluorouracil were compared after intravenous administration at a dose of 30 mg/kg to control Sprague-Dawley rats and to rats with diabetes mellitus induced by streptozotocin (DMIS). In DMIS rats, the area under the plasma concentration-time curve from time zero to time infinity (AUC) was significantly smaller (603 versus 909 microg min/ml) due to the significantly faster total body clearance (Cl; 47.8 versus 33.0 ml/min/kg). The faster Cl was due to the significantly faster renal (8.54 versus 4.02 ml/min/kg) and nonrenal (38.5 versus 28.7 ml/min/kg) clearances. In DMIS rats, the total amount of unchanged 5-fluorouracil excreted in 24 h urine was significantly greater (34.1% versus 13.0% of intravenous dose) due to the urine flow rate-dependent renal clearance of 5-fluorouracil in rats (the greater the urine flow rate, the greater the urinary excretion of 5-fluorouracil). Greater urinary excretion and a significantly smaller AUC resulted in a significantly faster Cl(r) in DMIS rats. The faster Cl(nr) in DMIS rats could be due to an increase in the expression and mRNA level of CYP1A1/2 in the rats. 相似文献
13.
Under hyperlipidemic conditions, there are likely to be alterations in the pharmacokinetics of CYP2C11 substrates following decreased expression of CYP2C11, which is homologous to human CYP2C9. The pharmacokinetics of tolbutamide (TB) and its metabolite 4‐hydroxy tolbutamide (4‐OHTB) were evaluated as a CYP2C11 probe after intravenous and oral administration of 10 mg/kg tolbutamide to poloxamer 407‐induced hyperlipidemic rats (HL rats). Changes in the expression and metabolic activity of hepatic CYP2C11 and the plasma protein binding of tolbutamide in HL rats were also evaluated. The total area under the plasma concentration–time curve ( AUC) of tolbutamide in HL rats after intravenous administration was comparable to that in controls due to their comparable non‐renal clearance ( CLNR). The free fractions of tolbutamide in plasma were comparable between the control and HL rats. The 4‐hydroxylated metabolite formation ratio ( AUC4‐OHTB/ AUCTB) in HL rats was significantly smaller than that in the control rats as a result of the reduced expression of hepatic CYP2C11 (by 15.0%) and decreased hepatic CLint (by 28.8%) for metabolism of tolbutamide to 4‐OHTB via CYP2C11. Similar pharmacokinetic changes were observed in HL rats after oral administration of tolbutamide. These findings have potential therapeutic implications, assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia. Since other sulfonylureas in clinical use are substrates of CYP2C9, their hepatic CLint changes have the potential to cause clinically relevant pharmacokinetic changes in a hyperlipidemic state. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
14.
Background and purpose:The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis. Experimental approach:Oltipraz was given intravenously (10 mg·kg −1) or orally (30 mg·kg −1) to rats with liver cirrhosis induced by N-dimethylnitrosamine (LC rats) or with diabetes, induced by streptozotocin (DM rats) or to rats with both liver cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A was measured using Western blot analysis. Key results:After i.v. or p.o. administration of oltipraz to LC and DM rats, the AUC was significantly greater and smaller, respectively, than that in control rats. In LCD rats, the AUC was that of LC and DM rats (partially restored towards control rats). Compared with control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats. Conclusions and implications:In rats with diabetes and liver cirrhosis, the AUC of oltipraz was partially restored towards that of control rats. 相似文献
15.
Ritonavir is one of several ketoconazole alternatives used to evaluate strong CYP3A4 inhibition potential in clinical drug–drug interaction (DDI) studies. In this study, four physiologically based pharmacokinetic (PBPK) models of ritonavir as an in vivo time‐dependent inhibitor of CYP3A4 were created and verified for oral doses of 20, 50, 100 and 200 mg using the fraction absorbed (F a) and oral clearance (CL oral) values reported in the literature, because transporter and CYP enzyme reaction phenotyping data were not available. The models were used subsequently to predict and compare the magnitude of the AUC increase in nine reference DDI studies evaluating the effect of ritonavir at steady‐state on midazolam (CYP3A4 substrate) exposure. Midazolam AUC and C max ratios were predicted within 2‐fold of the respective observations in seven studies. Simulations of the hepatic and gut CYP3A4 abundance after multiple oral dosing of ritonavir indicated that a 3‐day treatment with ritonavir 100 mg twice daily is sufficient to reach maximal CYP3A4 inhibition and subsequent systemic exposure increase of a CYP3A4 substrate, resulting in the reliable estimation of f m,CYP3A4. The ritonavir model was submitted as part of the new drug application for Kisqali® (ribociclib) and accepted by health authorities. 相似文献
16.
Omeprazole is a commonly used drug in patients with ulcerative colitis (UC). This study investigated the pharmacokinetics of omeprazole in rats with UC induced by dextran sulfate sodium (DSS). The pharmacokinetics of intravenously administered omeprazole (20 mg/kg) was investigated in normal and UC rats using LC-MS/MS. The formation of 5-OH omeprazole, a main metabolite of omeprazole, in rat liver microsomes (RLMs) from normal and UC rats was compared. The protein levels of CYP1A2, CYP2D1, and CYP3A1 in the liver were measured by Western blot. Compared with normal rats, UC rats had increased plasma concentrations of omeprazole, resulting in an increased AUC 0–240 min and decreased CL. DSS treatment decreased the formation rate of 5-OH omeprazole in RLMs but did not change the affinity of the enzymes. The V max and CL int of RLMs from UC rats were 62% and 48% those of RLMs from normal rats, respectively. The hepatic CYP1A2 and CYP3A1 protein levels in UC rats were 42.6 and 45.2% lower than those in normal rats, respectively; however, the protein levels of CYP2D1 in the two groups were similar. The activity and expression of some hepatic CYP450 isoforms were decreased by UC, leading to changes in the pharmacokinetics of omeprazole. 相似文献
17.
The pharmacokinetics of paclitaxel and docetaxel were compared in diabetic rats induced by streptozotocin (DMIS rats) and the impact of altered expression of cytochrome P450 3A (Cyp3A) and P‐glycoprotein (P‐gp) in the diabetic state. The pharmacokinetics of paclitaxel and docetaxel were determined after intravenous (5 mg/kg) and oral (30 and 40 mg/kg, respectively) administration to both groups and the mRNA expression levels of Cyp3A isozymes and Mdr1a and Mdr1b in the liver and small intestine were determined in control and DMIS rats. After intravenous administration, the AUC and clearance of paclitaxel and docetaxel were not significantly different in DMIS vs control rats. After oral administration, the AUC and Cmax of paclitaxel in DMIS rats were significantly greater than those in the control rats, whereas those of docetaxel was not changed significantly. The mRNA expression levels of hepatic Cyp3A1, Cyp3A9 and Mdr1b were significantly increased in DMIS compared with the control rats. In the intestine, Cyp3A62 expression decreased in the DMIS rats compared with the controls. Thus the pharmacokinetic changes of taxanes observed in the DMIS rats were attributed to changes in P‐gp and Cyp3A, predominant factors that control the absorption of paclitaxel and docetaxel, respectively. It seemed that there were different susceptibilities to intestinal P‐gp and Cyp3A between the two taxanes. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
18.
Effects of diabetes mellitus induced by streptozotocin (DMIS) on the pharmacokinetics of DA-7867 were investigated after i.v. and oral administration (10mg/kg) to control Sprague-Dawley rats and DMIS rats (at 7th and 29th days after administration of streptozotocin, 45mg/kg). After i.v. administration to DMIS rats, the AUC(0-infinity) values were significantly smaller (50.7 and 64.8% decrease for 7th and 29th days, respectively); this could be due to significantly faster Cl values in the rats (127 and 183% increase for 7th and 29th days, respectively). The faster Cl values were mainly due to significantly greater amount of unchanged drug excreted in 24-h urine (Ae(0-24h)). The greater Ae(0-24h) in DMIS rats could be due to urine flow rate-dependent renal clearance of DA-7867. After oral administration to DMIS rats, the AUC(0-infinity) values were also significantly smaller (61.3 and 72.6% decrease for 7th and 29th days, respectively); this could also be mainly due to significantly greater Ae(0-24h) in the rats. Streptozotocin-induced hepatotoxicity did not influence considerably on the pharmacokinetics of DA-7867 at 7th day when compared with those at 29th day. 相似文献
19.
Objectives It has been reported that mirodenafil is primarily metabolized via hepatic cytochrome P450 (CYP) 1A1/2, 2B1/2, 2D1 and 3A1/2 in rats. It has also been reported that the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 increases and that of hepatic CYP2D1 decreases in rats with acute renal failure induced by uranyl nitrate (U‐ARF rats). Thus, the pharmacokinetics of mirodenafil were studied in control and U‐ARF rats. Methods The pharmacokinetic parameters of mirodenafil and SK3541 (a metabolite of mirodenafil) were compared after the intravenous and oral administration of mirodenafil at a dose of 20 mg/kg to U‐ARF and control rats. Key findings After interavenous administration of mirodenafil to U‐ARF rats, the total area under the concentration–time curve (AUC) of mirodenafil was significantly smaller (36.5% decrease) than controls, possibly due to the significantly faster non‐renal clearance (66.1% increase; because of increase in the protein expression of hepatic CYP3A1) than controls. After the oral administration of mirodenafil to U‐ARF rats, the AUC of mirodenafil was also significantly smaller (47.8% decrease) due to the increase in the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 compared with controls. Conclusions After both intravenous and oral administration of mirodenafil to U‐ARF rats, the AUC SK3541/AUC mirodenafil ratios were comparable with that in controls and this could be due to further metabolism of SK3541 in rats. 相似文献
20.
本研究以细胞色素P450(CYP)3A探针药物咪哒唑仑的系统清除率(CL s)为指标,评价有限采样法(LSS)预测肝脏CYP3A抑制状态的可行性。采用系列剂量的CYP3A选择性抑制剂酮康唑预处理大鼠,静脉注射咪哒唑仑(MDZ)后若干时间点收集血浆样品并检测MDZ浓度,经逐步回归分析和Jack-knife验证建立LSS模型。对经相同处理的另一随机群体进行验证分析,评价该LSS模型方程的准确性和重现性。通过绘制Bland-Altman散点图对由两点(60和90 min)或三点(30、60和90 min,或30、60和120 min)血浆药物浓度建立的LSS预测模型得到的CL s估计值(CL est)与二房室模型拟合值(观察值,CL obs)进行偏差分析并计算95%可信区间,表明两种方法得到的CL s具有较好的一致性,LSS法预测误差小,特别是两点LSS预测模型更为准确且简便。结果表明:以咪哒唑仑清除率为指标,采用有限采样法评价大鼠肝脏CYP3A抑制状态下的代谢活性是一种准确而简便的方法,为今后推广到临床评价肝脏代谢功能从而制定和调整治疗药物的给药方案提供了理论依据和实验室证据。 相似文献
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